Eli, a sophomore studying Biology at Vassar College, worked to create models of gene-environment interactions between schizophrenia risk factors.
Schizophrenia is a psychiatric neurodevelopmental disorder with high heritability characterized by impairments in perception, cognition, and motivation. BSRP gave me the support to do the best science I could this summer. My mentor and the entire program were incredibly committed to helping me succeed as a scientist, a leader, and as a person. Although the specific pathogenic mechanisms of schizophrenia are unknown, previous work has identified genetic and environmental risk factors. To understand how these factors contribute to this disease, we sought to develop an in vitro model of a genetic risk factor and an in vivo model of an environmental risk factor. Recent studies have identified overexpression of complement component 4 (C4), a protein involved in synaptic pruning during development, as implicated in schizophrenia risk. Interestingly, overexpression of the C4A isoform correlates with an increased risk of developing schizophrenia, but overexpression of the C4B isoform does not. Understanding the differences in their functional roles will help determine the underlying pathogenic mechanisms of schizophrenia. C4 is highly expressed in astrocytes; therefore, we generated primary astrocyte cultures to identify differences between these isoforms from C4A-overexpressing and C4B-overexpressing mouse strains. To model environmental risk, we examined the expression of several stress-related markers in socially isolated mice and their group-housed controls. We monitor neuroimmune responses of astrocytes and microglia to stress, including expression of C4 and other complement factors. Future work will combine conclusions from these experiments by 1) co-culturing C4-overexpressing astrocytes with other cell types altered by stress and 2) using the C4A- and C4B-overexpressing mice in social isolation experiments to see how genetic and environmental risk factors interact. This research will lay the foundation for therapeutic advancement in treating underlying causes of schizophrenia.
Project: In vitro and in vivo assessment of neuroimmune risk factors for schizophrenia
Mentors: Cherish Taylor & Matthew Johnson
PI: Stevens Lab, Stanley Center for Psychiatric Research